Siglecs in the Porcine Oviduct: Roles in the Sperm Reservoir and Sperm Immune Response

猪输卵管中的 Siglecs：在精子库和精子免疫反应中的作用

• 批准号: 10607761
• 负责人: Leonardo Molina
• 金额: $ 4.28万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-26 至 2026-03-25
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10607761
• 关键词: Address; Adhesions; Affinity; Binding; Biochemical; Biological; Biological Assay; Cell Line; Cells; Chemotaxis; Complex; Contraceptive methods; Data; Deposition; Development; Diagnosis; Educational workshop; Embryonic Development; Environment; Epithelial Cells; Epithelium; Faculty; Family suidae; Female; Fertility; Fertilization; Gene Expression; Genomic approach; Germ Cells; Glycobiology; Glycoconjugates; Glycolipids; Goals; Grant; Hamsters; Hour; Illinois; Immune; Immune response; Immune system; Immunohistochemistry; Immunology; Immunosuppression; In Vitro; Infiltration; Innate Immune Response; Insemination; Knock-out; Knowledge; Learning; Lectin; Leucocytic infiltrate; Leukocyte Chemotaxis; Ligands; Location; Longevity; Mammalian Oviducts; Mammals; Mass Spectrum Analysis; Measures; Mediating; Mediator; Mentors; Migration Assay; Modeling; Molecular; Neuraminidase; Organ; Outcome; Phagocytes; Polysaccharides; Proteins; Rattus; Regulation; Reproduction; Reproductive Biology; Research; Research Training; Resources; Role; Science; Scientist; Sialic Acids; Site; Structure; Surface; System; Techniques; Testing; Tissues; Training; Tube; Universities; Uterus; Writing; career; career development; cell type; contraceptive target; data management; experience; experimental study; gamete transport; idiopathic infertility; immunoregulation; in vivo; in vivo Model; innovation; insight; interdisciplinary approach; male; novel; novel strategies; practical application; prevent; professor; programs; receptor; reproductive tract; response; responsible research conduct; senior faculty; sialic acid binding Ig-like lectin; sialoadhesin; sialylation; sperm cell; success; sugar; transcription factor; transcriptome sequencing

Project Summary/Abstract Siglecs in the Porcine Oviduct: Roles in the Formation of the Sperm Reservoir and Sperm Immune Response In mammals, only a small fraction of the deposited spermatozoa in the female reproductive tract reach the oviduct. Once in the oviduct, sperm bind to the oviductal epithelium, forming the functional sperm reservoir, which is crucial in prolonging sperm lifespan by inducing sperm into a quiescent state and providing these foreign gametes with an immune-suppressed environment. Siglecs are immunomodulatory receptors that recognize sialic acid-containing glycoconjugates. Using the pig as a model, we have discovered the presence of up to eight different Siglecs in the porcine oviduct, five of which are immune inhibitory. We have also characterized the N- and O-glycans and glycolipids present in porcine spermatozoa. Our results have identified the presence of several sialic acid-containing glycoconjugates on porcine sperm that are ligands for Siglecs. We hypothesize that the interactions of sialylated glycans of sperm with Siglecs from the oviduct are essential for sperm adhesion to the epithelium and sperm survival by suppressing leukocyte infiltration and the local innate immune response. The overall goal of this study is to develop a clear understanding of the role of Siglecs in the oviduct and sperm sialic acids during the formation of the sperm reservoir. The Specific Aims are 1) to determine the cellular location and abundance of Siglecs in the oviduct epithelium and sialic acid terminating glycans on sperm, 2) to determine the role of Siglec-1 and other Siglecs in sperm adhesion to oviduct cells, and 3) to determine the role of oviduct Siglecs in local immune regulation upon sperm-oviduct interactions. To address these aims I will utilize a combination of biochemical, cell and molecular, biological, and genomic approaches along with both in-vitro and in-vivo models. The findings from this study have practical applications such as enhanced diagnosis of idiopathic infertility and the development of novel approaches to regulating fertility such as the discovery of new contraceptive targets. This research training plan will provide me with training in a variety of cutting-edge and foundational techniques using an interdisciplinary approach that includes reproduction, immunology, and glycobiology. Moreover, it will support opportunities for career development to prepare me for a successful career in science. The outstanding scientific environment of the University of Illinois will provide me with multiple learning opportunities and the resources to accomplish this study. Dr. Miller, with proven mentoring experience and expertise in the study of the sperm-oviduct interaction, as well as my co-sponsors Dr. McKim and Dr. Nowak, will guide me in the success of the proposed research training plan and my scientific career development.

项目摘要/摘要 猪卵巢中的西格莱克：在形成精子和精子免疫中的作用 回复 在哺乳动物中，只有一小部分沉积的精子在女性生殖道中 输卵管。进入输卵管后，精子与卵形上皮结合，形成功能性精子储层， 这对于延长精子寿命至关重要，通过将精子诱导到静止状态并提供这些精子 具有免疫抑制环境的外国配子。 Siglecs是免疫调节受体 识别含有唾液酸的糖缀合物。使用猪作为模型，我们发现了存在 猪输卵管中最多八个不同的siglecs，其中五个是免疫抑制性的。我们也有 表征了猪精子中存在的N-和O-聚糖和糖脂。我们的结果已经确定 在猪精子上存在几种含有唾液酸的糖缀合物，它们是siglecs的配体。 我们假设精子的闪烁的糖糖与来自卵形的siaper糖糖的相互作用是必不可少的 通过抑制白细胞浸润和局部的精子粘附于上皮和精子生存 先天免疫反应。这项研究的总体目标是对 精子储层形成期间的输卵管和精子唾液酸中的siglecs。具体目的是 1）确定siglecs在产卵和唾液酸中的细胞位置和丰度 终止精子上的聚糖，2）确定Siglec-1和其他SIGLEC在精子粘附中的作用 Oviduct细胞和3）确定Oviduct Siglecs在局部免疫调节中的作用 互动。为了解决这些目标，我将利用生化，细胞和分子，生物学， 以及基因组方法以及体外和体内模型。这项研究的发现有 实际应用，例如增强特发育不育症的诊断和新颖的发展 调节生育能力的方法，例如发现新的避孕靶标。 该研究培训计划将为我提供各种尖端和基础的培训 采用跨学科方法的技术，包括生殖，免疫学和糖生物学。 此外，它将为职业发展的机会提供支持，以使我为成功的科学事业做好准备。 伊利诺伊大学的杰出科学环境将为我提供多次学习 机会和完成这项研究的资源。米勒博士，拥有经验丰富的指导经验和 精子互动研究的专业知识，以及我的共同赞助者McKim博士和Nowak博士， 将指导我取得拟议的研究培训计划和我的科学职业发展的成功。